The effects of hormones (somatomedins, insulin, tri-iodothyronine (T3), prostaglandins, etc.) and substrates on the control of cartilage growth and maturation will be studied using cartilage from 10 to 12 day old chicken embryos in organ culture as the model system. Specific emphasis will be placed on elucidating the mechanisms by which somatomedins, insulin and T3 exert their effects on the synthesis of macromolecules. The role of free fatty acids as inhibitors of somatomedin stimulation of cartilage macromolecule synthesis and prostaglandin A as an inhibitor of both basal and stimulated states will be further defined. The role of cyclic AMP as a second messenger and its mechanism of action in regulating cartilage metabolism will be delineated. Additional investigations will be undertaken with transplantable rat and mouse chondrosarcomas to determine the effect of malignant transformation on the hormonal regulation of chondrocytes.